KR100913984B1 - 플라비바이러스 감염 예방용 핵산 백신 - Google Patents
플라비바이러스 감염 예방용 핵산 백신 Download PDFInfo
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- KR100913984B1 KR100913984B1 KR1020037013021A KR20037013021A KR100913984B1 KR 100913984 B1 KR100913984 B1 KR 100913984B1 KR 1020037013021 A KR1020037013021 A KR 1020037013021A KR 20037013021 A KR20037013021 A KR 20037013021A KR 100913984 B1 KR100913984 B1 KR 100913984B1
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Abstract
Description
플라스미드 DNAb | 생쥐 # | DEN-2 바이러스에 대한 ELISA | DEN-2 바이러스에 대한 PRNTa 종말점 역가 9주, p.v. | JE 바이러스에 대한 PRNTa 종말점 역가 9주, p.v. | ||||
스크린 3주, p.v.c | 스크린 6주, p.v.c | 종말점 역가 9주, p.v. | ||||||
1:100 | 1:400 | 1:100 | 1:400 | |||||
pCB8D2-2J-2-9-1 | 풀, 1,2,4-10 | NDd | ND | + | + | 64,000 | ND | ND |
1 | + | + | + | + | 64,000 | >1000 | <2 | |
2 | + | + | + | + | 32.000 | >1000 | <2 | |
4 | + | + | + | + | 16,000 | 200 | <2 | |
5 | + | + | + | + | 4,000 | <10 | <2 | |
6 | + | + | + | + | 16,000 | 200 | <2 | |
7 | + | - | + | + | 64,000 | 100 | <2 | |
8 | + | - | + | + | 8,000 | 40 | <2 | |
9 | + | + | + | + | 6,400 | <2 | <4 | |
10 | + | + | + | + | 64,000 | >1000 | <2 | |
pCB9D2-1J-4-3 | 풀, 1-10 | ND | ND | + | + | 1,000 | ND | <2e |
1 | - | - | + | - | 400 | <10 | ND | |
2 | + | - | + | + | 200 | <10 | ND | |
3 | + | + | + | + | 4,000 | <2 | ≤4 | |
4 | + | - | + | - | 200 | <10 | ND | |
5 | - | - | + | + | 400 | <10 | ND | |
6 | + | + | + | + | 4,000 | <2 | 2 | |
7 | - | +/- | - | - | 100 | <10 | ND | |
8 | - | - | - | - | 200 | <10 | ND | |
9 | + | - | + | - | 4,000 | <2 | <2 | |
10 | - | - | + | + | 4,000 | <2 | <2 | |
pCBD2-14-6 | 풀, 1-10 | ND | ND | + | - | 200 | <2f | <2g |
1 | - | - | - | - | 400 | <10 | ND | |
2,3,6-9 | - | - | - | - | <100 | ND | ND | |
4 | + | + | + | + | 1,000 | <2 | <2 | |
5 | - | - | + | - | 2,000 | 8 | <2 | |
10 | + | - | - | - | <100 | ND | ND | |
pEGFP | 풀, 1-10 | - | ND | - | ND | <100 | <2 | <2 |
플라스미드 | IFAa | Ag-포획 ELISA 역가 | DEN-2에 대한 ELISA 역가b | DEN-2 PRNTc | |||
+/- | 구형/퍼짐 | 분비된 항원 | 소수성 막 단백질 조성물 | ≥1:100인 혈청의 수 | 풀링된 혈청 역가 | ≥1:10인 혈청의 수 | |
pCB8D2-2J-2-9-1 | + | 퍼짐 | 1:640 | 1:80 | 9/9 | 1:64000 | 7/9d |
pCB9D2-1J-4-3 | + | 구형 | <1:10 | 1:80 | 10/10 | 1:1000 | 0/10 |
pCBD2-14-6 | + | 구형 | <1:10 | 1:160 | 3/10 | 1:200 | 0/10 |
Claims (56)
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- 제1 플라비바이러스의 구조 단백질의 신호 서열 및 면역원성 플라비바이러스 항원을 코딩하는 전사 단위를 포함하고, 상기 항원은 제2 플라비바이러스로부터 유래하고, 또는 상기 항원은 하나 이상의 플라비바이러스로부터 유래하는 아미노산 서열을 포함하는 키메라 항원이고, 상기 전사 단위는 상기 항원의 합성을 지시하는 것을 특징으로 하는 분리된 핵산으로서, 상기 분리된 핵산은 DNA인 것이고, 상기 신호 서열은 서열번호 14 또는 서열번호 27의 뉴클레오티드 서열로 표시되는 조작된 일본 뇌염 바이러스 신호 서열이고, 상기 면역원성 플라비바이러스 항원은 황열 바이러스, 뎅기 혈청형 1 바이러스, 뎅기 혈청형 2 바이러스, 뎅기 혈청형 3 바이러스, 뎅기 혈청형 4 바이러스, 일본 뇌염 바이러스, 포와산 바이러스, 세인트 루이스 뇌염 바이러스 및 웨스트 나일 바이러스로 이루어지는 군으로부터 선택되는 플라비바이러스 항원인 것이고, 상기 항원은 M 단백질, E 단백질, M 단백질과 E 단백질 둘다, M 단백질의 일부분, E 단백질의 일부분, M 단백질의 일부분과 E 단백질의 일부분 둘다, 또는 이들의 조합으로 이루어지는 군으로부터 선택되고, 상기 분리된 핵산은 서열번호 15, 서열번호 19, 서열번호 21, 서열번호 23, 서열번호 44 및 서열번호 46으로 이루어지는 군으로부터 선택되는 뉴클레오티드 서열을 포함하는 것을 특징으로 하는 분리된 핵산.
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- 제11항의 핵산을 포함하고, 제11항의 상기 면역원성 플라비바이러스 항원을 발현하고 분비하는 포유동물 세포.
- 제11항의 핵산과 약제학적으로 허용가능한 담체를 포함하는 조성물의 효과적인 양을 인간을 제외한 개체에게 투여하는 단계를 포함하는, 플라비바이러스에 의한 감염에 대항하여 인간을 제외한 개체를 면역화하는 방법.
- 플라비바이러스에 의한 감염에 대항하여 개체를 면역화하기 위한, 제11항의 핵산과 약제학적으로 허용가능한 담체를 포함하는, 플라비바이러스의 감염의 예방 또는 치료를 위한 조성물.
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- 제18항에 있어서, 상기 플라비바이러스 항원은 M 단백질과 E 단백질 둘다이고, 상기 개체의 체내의 세포는 상기 핵산이 세포 내에 삽입된 후에, 상기 M 단백질과 상기 E 단백질을 포함하는 서브바이러스 입자를 분비하는 것을 특징으로 하는 조성물.
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- 제18항에 있어서, 상기 조성물은 개체에 1회 투여량 (single dose)으로 투여되는 것을 특징으로 하는 조성물.
- 제18항에 있어서, 상기 조성물은 비경구 경로를 통하여 투여되는 것을 특징으로 하는 조성물.
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- 제11항의 핵산으로부터 생산된 항원.
- (a) 항원/항체 복합체가 형성될 수 있는 조건하에서 시료를 제38항의 항원과 접촉시키는 단계; 및(b) 항원/항체 복합체 형성을 검출하여, 상기 시료 중의 플라비바이러스 항체를 검출하는 단계를 포함하는, 시료 중의 플라비바이러스 항체를 검출하는 방법.
- 제38항의 항원을 가지고 면역화에 반응하여 생산된 항체.
- (a) 항원/항체 복합체가 형성될 수 있는 조건하에서 시료를 제40항의 항체와 접촉시키는 단계; 및(b) 항원/항체 복합체 형성을 검출하여, 시료 중의 플라비바이러스 항원을 검출하는 단계를 포함하는, 시료 중의 플라비바이러스 항원을 검출하는 방법.
- (a) 항원/항체 복합체가 형성될 수 있는 조건하에서 인간을 제외한 개체로부터 얻은 시료를 제38항의 항원과 접촉시키는 단계; 및(b) 항원/항체 복합체 형성을 검출하여, 상기 인간을 제외한 개체의 플라비바이러스 감염을 진단하는 단계를 포함하는, 인간을 제외한 개체의 플라비바이러스 감염을 진단하는 방법.
- (a) 항원/항체 복합체가 형성될 수 있는 조건하에서 인간을 제외한 개체로부터 얻은 시료를 제40항의 항체와 접촉시키는 단계; 및(b) 항원/항체 복합체 형성을 검출하여, 상기 인간을 제외한 개체의 플라비바이러스 감염을 진단하는 단계를 포함하는, 인간을 제외한 개체의 플라비바이러스 감염을 진단하는 방법.
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Applications Claiming Priority (3)
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US09/826,115 | 2001-04-04 | ||
US09/826,115 US7227011B2 (en) | 1998-06-04 | 2001-04-04 | Nucleic acid vaccines for prevention of flavivirus infection |
PCT/US2002/010764 WO2002081754A1 (en) | 2001-04-04 | 2002-04-04 | Nucleic acid vaccines for prevention of flavivirus infection |
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KR20030092051A KR20030092051A (ko) | 2003-12-03 |
KR100913984B1 true KR100913984B1 (ko) | 2009-08-25 |
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US (6) | US7227011B2 (ko) |
EP (3) | EP1935991B1 (ko) |
JP (2) | JP4448281B2 (ko) |
KR (1) | KR100913984B1 (ko) |
CN (2) | CN101002936A (ko) |
BR (1) | BRPI0208301B8 (ko) |
CA (1) | CA2443323C (ko) |
HK (1) | HK1062836A1 (ko) |
MX (1) | MXPA03008838A (ko) |
NZ (1) | NZ529106A (ko) |
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